沉默两个基因足以将间充质干细胞变为癌起始细胞（附原文）

sunsong7

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+ ~$ r$ Q! h/ T+ U" ?0 o1 i7 U1 xTargeted methylation of two tumor suppressor genes is sufficient to transform mesenchymal stem cells into cancer stem/initiating cells ( L; a2 W2 d4 c! S; _; W0 @
甲基化沉默两个肿瘤抑制基因足以将间充质干细胞变为癌起始细胞（CSC，CIC）
! U! E$ b! E7 mCancer research http://cancerres.aacrjournals.or ... AN-10-3418.abstract( _% Y% D- V8 E/ f% K! O  R- j

6 C5 y  j( E7 q9 T# g5 LI-Wen Teng1, Pei-Chi Hou1, Kuan-Der Lee2, Pei-Yi Chu3, Kun-Tu Yeh4, Victor X. Jin5, Min-Jen Tseng1, Shaw-Jenq Tsai6, Yu-Sun Chang Dr.7, Chi-sheng Wu8, H. Sunny Sun9, Kuen-daw Tsai10, Long-Bin Jeng10, Kenneth P. Nephew11, Tim H. M. Huang12, Shu-Huei Hsiao13, , and Yu-Wei Leu14
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7 M2 i- _0 Z/ }1 a$ L( D6 U4 R1Department of Life Science, National Chung Cheng University , [# p6 t: ^, g  W5 f
2Hematology and Oncology, Chang Gung Memorial Hospital
' M* y* l* P3 U  p# g* I: R% D! A1 q3Pathology, ChangHua Christian Hospital + r4 k/ p$ J, Y/ i" d5 _
4Department of Pathology, Changhua Christian Hospital ) u8 r3 }5 o3 G% d5 q3 N# |. `/ }
5Biomedical Informatics, The Ohio State University , T+ |& H5 x2 g& k$ Y
6Department of Physiology, National Cheng Kung University
" _; W) S8 b- D7Graduate Institute of Basic Medical Sciences, Chang-Gung University
, T' w5 ~: U, W3 @( x" E5 e, H5 A8Molecular Medicine Research Center, Chang Gung University
; {. H6 M  W; H' W+ z, C9National Cheng-Kung University Medical College, Institute of Molecular medicine 6 C- e. D0 W: j% T& K
10Department of Internal Medicine, China Medical University Peikang Hospital
+ k0 L* ]) R) K. H6 r3 V11Cellular and Integrative Physiology, Indiana University 5 L. @0 T- y+ H' ?( o- M( h  P
12Human Cancer Genetics, MVIMG Dept, The Ohio State University 4 C/ R2 k5 f# O
13Life Science, National Chung Cheng University
- q) p/ o* T( o+ z* P: s14Chung-Cheng University 2 t7 p8 ~5 t  ]1 s! H4 A& f& O- r9 Y
Corresponding Author:
, [$ O& d6 M6 OShu-Huei Hsiao, Life Science, National Chung Cheng University, 168 University Road, Min Hsiung, Chia-Yi, 621, Taiwan bioshh@ccu.edu.tw
# V, ?4 G1 E& w! v3 f, ~9 hAbstract+ {9 x; G9 @% t$ u9 [
Although DNA hypermethylation within promoter CpG islands is highly correlated with tumorigenesis, it has not been established whether DNA hypermethylation within a specific tumor suppressor gene (TSG) is sufficient to fully transform a somatic stem cell. In this study, we addressed this question using a novel targeted DNA methylation technique to methylate the promoters of HIC1 and RassF1A, two well-established TSGs, along with a two-component reporter system to visualize successful targeting of human bone marrow-derived mesenchymal stem cells (MSC) as a model cell system. MSCs harboring targeted promoter methylations of HIC1/RassF1A displayed several features of cancer initiating/cancer stem cells, including loss of anchorage dependence, increased colony formation capability, drug resistance and pluripotency. Notably, inoculation of immunodeficient mice with low numbers of targeted MSC resulted in tumor formation, and subsequent serial xenotransplantation and immunohistochemistry confirmed the presence of stem cell markers and MSC lineage in tumor xenografts. Consistent with the expected mechanism of TSG hypermethylation, treatment of the targeted MSC with a DNA methyltransferase inhibitor reversed their tumorigenic phenotype. To our knowledge, this is the first direct demonstration that aberrant TSG hypermethylation is sufficient to transform a somatic stem cell into a fully malignant cell with cancer initiating/cancer stem properties. $ n0 ^/ y7 e1 k. c. X
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Received September 17, 2010.
! l& i, Y! e0 x5 p& w6 G" |Revision received March 27, 2011. ( |4 ~- z2 q: J* o" z
Accepted April 18, 2011. / l/ `9 M" i. r% w1 x
Copyright © 2011, American Association for Cancer Research. " q/ \" Z0 u' L. E. F

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6楼原文 感谢apengforever 提供

sunsong7

Tumor Suppressor Methylation is Cause for Cancer Concern ( S6 v7 ~# H$ w: G6 g  u" [+ G1 t
http://www.epigenie.com/Headline ... e-cancer-cells.html2 ^$ A0 r8 P* D5 m  p$ o" k# p
May 2, 2011 Aberrant DNA methylation causes cancer.  Wait, didn’t we know this already? Well, not exactly. Association and causation are two very different things. For instance, being smart may be associated with wearing glasses, but the actual cause is a desire to not bump into everything.
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( L# p. u1 n8 p6 J) N9 _ In order to determine whether aberrant DNA methylation at particular loci can play a causal role in tumorigenesis, a team of researchers from Taiwan and Ohio developed a novel method.  Here is how they did it and what they found:
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Using Targeted DNA Methylation (TDM), they recruited DNA methyltransferases (DNMTs) to specific loci by introducing methylated DNA complementary to the target.
" p! h' a0 F% Z( h2 s& rConcurrent DNA methylation at tumor suppressor genes RASSF1A and HIC1 in human mesenchymal stem cells (MSCs) resulted in the acquisition of cancer initiating/cancer stem cell features both in vitro and in a xenograft model. ; F! x  ?( C0 s( O
The transformed cells had genome-wide changes in DNA methylation and altered p53 function.  2 z) [( D& f4 W# \( X0 Q
The tumorigenic phenotype was reversed by treatment with a DNMT inhibitor.
+ C) q9 H! }5 i& v5 c2 FThis is the first demonstration that silencing of particular tumor suppressor genes (TSGs) by aberrant DNA methylation can directly cause somatic stem cells to transform into cancer stem cell (CSC)-like cells.  Hopefully their findings will finally and heritably silence the critics.% ?: g$ p0 T+ O/ u# H# R

/ v  l* Z  Y- c6 s) Y9 lDetermine whether there is a causal link for yourself at Cancer Research, April 2011.
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**Find out how to get highly sensitive methylated DNA capture with New England Biolab's EpiMarkTM Methylated DNA Enrichment Kit.% @# l% X0 ^9 @6 q

tjutiger

好文章！！强烈求原文！！！！！谢谢！！！

shqinzhu

求原文

wys7416

反过来说，把癌细胞中激活抑癌基因，是不是应该也可以把癌细胞转化成正常细胞了？

apengforever

,这不错，可以做为一个不错的方法来研究别的，呵呵

大笨鸟

谢谢分享
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bid

谢谢

duanhf

谢谢分享，辛苦了

duanhf

谢谢分享，辛苦了